1. Field of the Invention
This invention concerns a method of determining liver function on the basis of a plasma elimination rate and a device for determining liver function on the basis of a plasma elimination rate.
2. The Prior Art
Liver function is an important parameter in intensive care medicine and plays a crucial role in determining the prognosis for extremely ill patients. At the present time, liver function is determined routinely in intensive care medicine on the basis of various laboratory parameters which characterize the synthesis performance and the elimination performance of the liver. However, the disadvantage of these laboratory values is that when liver function fails, these values do not become pathological until after a rather long latency period, so the liver dysfunction does not become evident for several days.
One possibility of evaluating liver function immediately, at least with regard to elimination performance, consists of administering indicator substances which are eliminated through the liver and determining the elimination time constant of these indicators. Indocyanine green is a common indicator used for this purpose. Indocyanine green is usually injected intravenously as a bolus, and then at least two blood samples, preferably several blood samples are taken at intervals of several minutes over a period of at least 15 minutes following the bolus injection. The elimination time constant can be calculated from the drop in indicator dye concentration in the blood specimens. However, this method is rarely used in clinical practice because it is still too time consuming because of the laboratory analyses.
The object of this invention is to create a method and a device with which liver function can be determined by non-invasively and the measurement result is available more rapidly.
The method and the device according to this invention measure a reduction in indicator concentration in the blood which occurs due to degradation of the indicator by the liver. After injecting a suitable indicator such as indocyanine green, into the bloodstream, a characteristic indicator concentration-time curve is obtained at a measurement point in the body when liver function is normal. First there is an initial maximum indicator concentration, and after a temporary decline, there is a second maximum indicator concentration. The second maximum occurs due to recirculation, i.e., a second pass is already occurring even before the concentration surge declines in the first pass.
An average circulation transit time mttcirc is calculated from the measurement of the curve of the indicator concentration over time c(t), and in addition, a parameter k representing a fractional recovery rate of the indicator dye after each pass through the circulation is also determined. Then with these values, the plasma elimination rate (PER) can be calculated according to the equation:
PER=(1xe2x88x92k)/(kxc2x7mttcirc)
The result is available after only a few recirculation cycles.
The average circulation transit time mttcirc given above can be calculated from a circulation transport function g(t) which describes the transport behavior of the circulation. The average circulation transit time mttcirc is then obtained according to the equation:       mtt    circ    =                    ∫        0        ∞            ⁢                                    g            ⁡                          (              t              )                                ·          t                ⁢                  xe2x80x83                ⁢                  ⅆ          t                                    ∫        0        ∞            ⁢                        g          ⁡                      (            t            )                          ⁢                  xe2x80x83                ⁢                  ⅆ          t                    
The circulation transport function g(t) can be calculated from the measured indicator concentration with the help of an iterative nonlinear fitting method. In this method, with the stipulation of a model function:
g(t)=amgm(t)+am+1gm+1(t)+ . . . +angn(t)
with                     ∑                  m          =          1                n            ⁢              xe2x80x83            ⁢      am        =    1    ,
where the individual compartments amgm are described by left-skewed distribution functions, a recursive convolution is performed according to the equations:
xe2x80x83c(t)=cbolus(t)+crez(t)
and             c      rez        ⁡          (      t      )        =      k    ·                  ∫        0        t            ⁢                                    g            ⁡                          (                              t                -                u                            )                                ·                      c            ⁡                          (              u              )                                      ⁢                  xe2x80x83                ⁢                  ⅆ          u                    
where the parameters k, am and the parameters of the distribution functions are optimized by the method of the least squares deviation, with at least one compartment a1g1(t) being stipulated. In the equation, c(t) represents the concentration-time curve of the indicator dye, cbolus(t) represents the first portion of the indicator concentration-time curve fitting directly to the measurement site, crez(t) denotes a recirculating portion of the indicator concentration-time curve and k denotes the elimination fraction of the indicator eliminated through the liver.
For a greater accuracy, two compartments (a1g1(t)) and (a2g2(t)) can be stipulated.
As an alternative, the optical measurement of the resulting indicator concentration in the bloodstream can be performed by fiber optic measurement in a central vessel or as a non-invasive method by measuring the light transmission or reflection of incident light at suitable body locations, in particular on the finger, earlobe, bridge of the nose, the forehead or the inside of the cheek (buccal mucosa).